Rajao Daniela S, Loving Crystal L, Waide Emily H, Gauger Phillip C, Dekkers Jack C M, Tuggle Christopher K, Vincent Amy L
Virus and Prion Diseases of Livestock Research Unit, National Animal Disease Center, USDA, ARS, Ames, IA, USA.
J Innate Immun. 2017;9(2):193-202. doi: 10.1159/000451007. Epub 2016 Dec 17.
Influenza A viruses (IAV) infect many host species, including humans and pigs. Severe combined immunodeficiency (SCID) is a condition characterized by a deficiency of T, B, and/or natural killer (NK) cells. Animal models of SCID have great value for biomedical research. Here, we evaluated the pathogenesis and the innate immune response to the 2009 H1N1 pandemic IAV (H1N1pdm09) using a recently identified line of naturally occurring SCID pigs deficient in T and B lymphocytes that still have functional NK cells. SCID pigs challenged with H1N1pdm09 showed milder lung pathology compared to the non-SCID heterozygous carrier pigs. Viral titers in the lungs and nasal swabs of challenged SCID pigs were significantly higher than in carrier pigs 7 days postinfection, despite higher levels of IL-1β and IFN-α in the lungs of SCID pigs. The lower levels of pulmonary pathology were associated with the T and B cell absence in response to infection. The higher viral titers, prolonged shedding, and delayed viral clearance indicated that innate immunity was insufficient for controlling IAV in pigs. This recently identified line of SCID pigs provides a valuable model to understand the immune mechanisms associated with influenza protection and recovery in a natural host.
甲型流感病毒（IAV）可感染包括人类和猪在内的多种宿主物种。重症联合免疫缺陷（SCID）是一种以T细胞、B细胞和/或自然杀伤（NK）细胞缺乏为特征的病症。SCID动物模型在生物医学研究中具有重要价值。在此，我们使用最近鉴定出的一种自然发生的SCID猪品系评估了对2009年甲型H1N1大流行病毒（H1N1pdm09）的发病机制和先天免疫反应，该品系猪缺乏T淋巴细胞和B淋巴细胞，但仍具有功能性NK细胞。与非SCID杂合子携带猪相比，用H1N1pdm09攻击的SCID猪表现出较轻的肺部病理变化。尽管SCID猪肺中IL-1β和IFN-α水平较高，但在感染后7天，受攻击的SCID猪肺和鼻拭子中的病毒滴度显著高于携带猪。较低水平的肺部病理变化与感染时T细胞和B细胞的缺失有关。较高的病毒滴度、延长的病毒脱落时间和延迟的病毒清除表明先天免疫不足以控制猪体内的IAV。最近鉴定出的这种SCID猪品系为了解自然宿主中与流感保护和恢复相关的免疫机制提供了一个有价值的模型。
